Additional Nodules Research Articles

Multiinstitutional Phase 2 Clinical Trial of Intraoperative Molecular Imaging of Lung Cancer

Intraoperative molecular imaging (IMI) may improve surgical outcomes during pulmonary resection for lung cancer. A multiinstitutional phase 2 IMI clinical trial was conducted using a near-infrared, folate receptor-targeted contrast agent for lung adenocarcinomas, OTL38. The primary goal was to determine whether OTL38 improved surgeons' ability to identify difficult to find nodules, occult cancers, and positive margins. Patients with lung nodules received OTL38 (0.025 mg/kg) preoperatively. Patients had IMI sequentially during lung inspection, tumor resection, and margin check. Efficacy was evaluated by occurrence of clinically significant events, occurrences that caused the surgeon to modify the operation or upstage the patient's cancer. Safety was assessed for a single intravenous dose of OTL38. Of 110 patients recruited, 92 were eligible for analysis. During lung inspection, IMI found 24 additional nodules, 9 (10%) of which were cancers that had not been known preoperatively. During tumor resection, IMI located 11 (12%) lesions that the surgeon could not find. During the margin check, IMI revealed 8 positive margins (9%) that the surgeon thought were negative. Benefits of IMI were pronounced in patients undergoing sublobar pulmonary resections and in patients with ground-glass opacities. There were no serious adverse events. All surgeons felt comfortable with the procedures by 10 cases. In this phase 2 clinical trial, IMI improved outcomes for 26% of patients. A randomized, multiinstitutional phase 3 clinical trial is underway.

S3550 A Very Rare Primary Adenocarcinoma of the Duodenum

INTRODUCTION: Primary duodenal cancers are a rare occurrence among gastrointestinal malignancies. Cancers that occur within the duodenum include adenocarcinoma, neuroendocrine, lymphomas and leiomyosarcomas. Diagnosis is often delayed leading to worsening disease burden and poorer outcomes. We present an unusual case of a female with a history of triple negative invasive ductal carcinoma who was unfortunately found to have a primary adenocarcinoma of the duodenum. CASE DESCRIPTION/METHODS: The patient is a 61 year old female with a history of triple negative invasive ductal carcinoma status post mastectomy, radiation and chemotherapy who presented to her outpatient oncologist. Six years following her completed treatment, the patient developed symptoms of dyspepsia and iron deficiency anemia. She underwent CT imaging of the abdomen demonstrating duodenal obstruction and evidence of intrathoracic metastasis. The patient subsequently underwent push enteroscopy which revealed a duodenal mass. Duodenal stents were subsequently placed and biopsies taken intraoperatively. A PET scan was then performed and demonstrated hypermetabolic activity at the third and fourth portion of the duodenum with additional lung nodules consistent with metastasis. The biopsies resulted as a primary adenocarcinoma of the duodenum. The patient was started on oxaliplatin chemotherapy. Three months later a follow up PET scan was performed revealing interval improvement of the primary duodenal tumor and lung nodules. The patient continues to undergo palliative chemotherapy and has been consistently following up for her office visits. DISCUSSION: Primary duodenal cancer is a rare disease which reflects approximately 0.3–0.5% of all gastrointestinal malignancies. Adenocarcinoma commonly arises in the third and fourth portions of the duodenum. Most common presenting signs and symptoms include epigastric pain, anemia and weight loss. Since presenting symptoms are vague in nature, early diagnosis is often missed. One study found that at time of diagnosis, less than 40% could pursue curative resection. Tumor resectability and presence of metastasis have been regarded as the strongest factors influencing patient outcomes. One retrospective study demonstrated that patients who underwent tumor resection had a significantly longer survival rate compared to those who had no surgery. At the time of diagnosis, our patient demonstrated metastatic disease and therefore underwent palliative duodenal stenting and chemotherapy with oxaliplatin.

Efficacy of breast MRI for surgical decision in patients with breast cancer: ductal carcinoma in situ versus invasive ductal carcinoma

BackgroundPreoperative breast magnetic resonance imaging (MRI) provides more information than mammography and ultrasonography for determining the surgical plan for patients with breast cancer. This study aimed to determine whether breast MRI is more useful for patients with ductal carcinoma in situ (DCIS) lesions than for those with invasive ductal carcinoma (IDC).MethodsA total of 1113 patients with breast cancer underwent mammography, ultrasonography, and additional breast MRI before surgery. The patients were divided into 2 groups: DCIS (n = 199) and IDC (n = 914), and their clinicopathological characteristics and oncological outcomes were compared. Breast surgery was classified as follows: conventional breast-conserving surgery (Group 1), partial mastectomy with volume displacement (Group 2), partial mastectomy with volume replacement (Group 3), and total mastectomy with or without reconstruction (Group 4). The initial surgical plan (based on routine mammography and ultrasonography) and final surgical plan (after additional breast MRI) were compared between the 2 groups. The change in surgical plan was defined as group shifting between the initial and final surgical plans.ResultsChanges (both increasing and decreasing) in surgical plans were more common in the DCIS group than in the IDC group (P < 0.001). These changes may be attributed to the increased extent of suspicious lesions on breast MRI, detection of additional daughter nodules, multifocality or multicentricity, and suspicious findings on mammography or ultrasonography but benign findings on breast MRI. Furthermore, the positive margin incidence in frozen biopsy was not different (P = 0.138).ConclusionsPreoperative breast MRI may provide more information for determining the surgical plan for patients with DCIS than for those with IDC.

Vocal cordopathy consequent to bronchial asthma inhalation therapy

BackgroundVocal cords signify an imperative lane for air flow in and out of the respiratory tract along with a phonetic role. So, the aim of this work is to assess the impact of habitual versus occasional utilization of inhalation therapy of patients with bronchial asthma on their vocal cords regarding visual endoscopic pathological changes in addition to phonetic dysfunction. This study was conducted on 112 diagnosed bronchial asthma patients (66 male and 46 females). They were classified into the following: group A (habitual user), 65 patients with severe persistent asthma with regular frequent intake of inhalation therapy, and group B (occasional user), 47 patients with intermittent asthma with alternating intake of inhalation therapy. They were submitted to clinical, vocal assessment plus laryngoscopic examination.ResultsThe habitual users group demonstrated that laryngeal edema and hyperemia attained the higher percentage in the adult than children age group (60%, 40–67.3%, 50%) respectively together after 6 and 9 months of study followed by laryngeal nodules (5.4%, 0–9%, 10%). Occasional users presented the same findings comparable to the habitual group (27%, 10–32.4%, 20%). Cord paresis, cord dysfunction, and fungal plaques were in the second frequencies in both age groups with the same percentage (3.6%) at the end of the study; however, in occasional users, fungal plaques illustrated low percentage (2.7%, 5.4–0, 10%, respectively).ConclusionInhalation therapy as a form of asthma medication correlated with major counter effects on vocal cords with well-recorded laryngeal hyperemia, edema, and vocal nodules in addition to fungal plaques moreover phonetic dysfunction.

Analysis of Malignant Thyroid Nodules That Do Not Meet ACR TI-RADS Criteria for Fine-Needle Aspiration.

OBJECTIVE. Compared with other guidelines, the American College of Radiology (ACR) Thyroid Imaging Reporting and Data System (TI-RADS) has decreased the number of nodules for which fine-needle aspiration is recommended. The purpose of this study was to evaluate the characteristics of malignant nodules that would not be biopsied when the ACR TI-RADS recommendations are followed. MATERIALS AND METHODS. We retrospectively reviewed a total of 3422 thyroid nodules for which a definitive cytologic diagnosis, a definitive histologic diagnosis, or both diagnoses as well as diagnostic ultrasound (US) examinations were available. All nodules were categorized using the ACR TI-RADS, and they were divided into three groups according to the recommendation received: fine-needle aspiration (group 1), follow-up US examination (group 2), or no further evaluation (group 3). RESULTS. Of the 3422 nodules, 352 were malignant. Of these, 240 nodules were assigned to group 1, whereas 72 were assigned to group 2 and 40 were included in group 3. Sixteen of the 40 malignant nodules in group 3 were 1 cm or larger, and, on the basis of analysis of the sonographic features described in the ACR TI-RADS, these nodules were classified as having one of five ACR TI-RADS risk levels (TR1-TR5), with one nodule classified as a TR1 nodule, eight as TR2 nodules, and seven as TR3 nodules. If the current recommendation of no follow-up for TR2 nodules was changed to follow-up for nodules 2.5 cm or larger, seven additional malignant nodules and 316 additional benign nodules would receive a recommendation for follow-up. If the current size threshold (1.5 cm) used to recommend US follow-up for TR3 nodules was decreased to 1.0 cm, seven additional malignant nodules and 118 additional benign nodules would receive a recommendation for follow-up. CONCLUSION. With use of the ACR TI-RADS, most malignant nodules that would not be biopsied would undergo US follow-up, would be smaller than 1 cm, or would both undergo US follow-up and be smaller than 1 cm. Adjusting size thresholds to decrease the number of missed malignant nodules that are 1 cm or larger would result in a substantial increase in the number of benign nodules undergoing follow-up.

The Effect of Low Carbohydrate Diets on Preventing and Treating Carcinogen-Induced Lung Cancer in Mice

Abstract Objectives Since cancer cells typically rely more on glycolysis than normal cells, we hypothesized that lowering carbohydrate intake may reduce cancer risk. We aimed to investigate the efficacy of low-carbohydrate (CHO) diets in preventing and treating a tobacco-specific carcinogen-induced lung cancer in female A/J mice. Methods We evaluated the role of different types of CHO (easily digestible vs resistant), protein (casein vs. soy) and fat (fish vs. coconut vs. a mixture of oils) in modulating 4-(N-methyl-N-nitrosamino)-1-(3- pyridyl)-1-butanone (NNK)-induced lung nodule formation in these mice. To assess the efficacy of these diets in preventing NNK-induced lung nodule formation, we put these mice in the different diets for 2 weeks, intraperitoneally-injected NNK once a week for two weeks to initiate lung nodule formation. After 5 months, the lung nodules in these mice were counted. Results The lowering of easily digestible CHO significantly reduced constitutive blood glucose levels and lung nodule formation in the mice. Interestingly, diets low in easily digestible starch, high in fish oil (FO) and soy protein (15%Amylose/Soy/FO) were the most effective at preventing the formation of NNK-induced lung nodules. To determine if this 15%Amylose/Soy/FO is also effective at slowing tumor progression, we fed NNK-injected A/J mice a Western diet until tumors were established (5 months post NNK) and then either switched them to the 15%Amylose/Soy/FO or kept them on the Western diet for 5 additional months. The 15%Amylose/Soy/FO diet prevented the formation of additional lung tumor nodules and reduced the size of the tumors, although no significant difference was observed in tumor stage. The reduction in size of the lung tumors on the 15%Amylose/Soy/FO diet was not due to a lower tumor proliferation (Ki67 index) but an increase in apoptosis, as determined by TUNEL assays. Conclusions We conclude that a diet change that lowers glucose intake, incorporates FO and soy protein may be effective not only in preventing lung cancer formation but also in slowing the growth of established lung tumors. Funding Sources Lotte &amp; John Hecht Memorial Foundation.

MON-492 Should Isthmic Thyroid Nodule Be Included in ACR TI-RADS Points in Predicting Thyroid Cancer?

Background: Thyroid nodules are routinely evaluated with ultrasound. Isthmic nodules carry higher risk of malignancy (in press). Surgical studies suggest higher risk of metastasis from thyroid cancer located in isthmus region. In this study, we evaluate how adding an extra point for isthmic location to current ACR-TIRADS will affect the sensitivity and specificity to predict thyroid cancer.Methods: We performed a subanalysis of isthmic nodules contained in a retrospectively created database of 3313 adult patients from six referral centers with confirmed benign or malignant nodules. Sensitivity and specificity were calculated using the current ACR TI-RADS scoring system and compared to a system that would add an extra point based on nodule location in the isthmus.Results: There were 195 nodules in the isthmus (34 malignant). If a recommendation for FNA was considered a positive test result, the sensitivity and specificity would be 50% (17/34) and 61% (99/161) respectively using current ACR TI-RADS scoring. If an additional point was added the sensitivity and specificity would be 62% (21/34) and 36% (58/161) respectively. Adding the additional point would lead to detection of 4 additional malignant nodules at the cost of biopsying 41 additional benign nodules. If a recommendation for either FNA or follow-up ultrasound for 5 years was considered a positive test result, the sensitivity and specificity would be 82% (28/34) and 35% (56/161) respectively using current ACR TI-RADS scoring. If an additional point was added the sensitivity and specificity would be 94% (32/34) and 15% (24/161) respectively. Adding the additional point would lead to detection of 4 additional malignant nodules at the cost of either biopsying or following 32 additional benign nodules.Conclusions: Isthmic nodules are more likely to be malignant than nodules in other locations. When using the ACR TI-RADS, adding a point for isthmic nodules improves detection of cancer with a moderate increase in the rate of FNA and follow-up of benign nodules. Given the higher risk of extra thyroidal extension and nodal metastases for isthmic cancers, this tradeoff between sensitivity and specificity may be acceptable and should be considered when dealing with nodules in the isthmus.Keywords: thyroid nodule, ACR TI-RADS, location, isthmus, thyroid cancer

Pea Efficiency of Post-drought Recovery Relies on the Strategy to Fine-Tune Nitrogen Nutrition.

As drought is increasingly frequent in the context of climate change it is a major constraint for crop growth and yield. The ability of plants to maintain their yield in response to drought depends not only on their ability to tolerate drought, but also on their capacity to subsequently recover. Post-stress recovery can indeed be decisive for drought resilience and yield stability. Pea (Pisum sativum), as a legume, has the capacity to fix atmospheric nitrogen through its symbiotic interaction with soil bacteria within root nodules. Biological nitrogen fixation is highly sensitive to drought which can impact plant nitrogen nutrition and growth. Our study aimed at dynamically evaluating whether the control of plant N status after drought could affect nodulated pea plant’s ability to recover. Two pea genotypes, Puget and Kayanne, displaying different drought resilience abilities were compared for their capacity to tolerate to, and to recover from, a 2-weeks water-deficit period applied before flowering. Physiological processes were studied in this time-series experiment using a conceptual structure–function analysis framework focusing on whole plant carbon, nitrogen, and water fluxes combined to two 13CO2 and 15N2 labeling experiments. While Puget showed a yield decrease compared to well-watered plants, Kayanne was able to maintain its yield. During the recovery period, genotype-dependent strategies were observed. The analysis of the synchronization of carbon, nitrogen, and water related traits dynamics during the recovery period and at the whole plant level, revealed that plant growth recovery was tightly linked to N nutrition. In Puget, the initiation of new nodules after water deficit was delayed compared to control plants, and additional nodules developed, while in Kayanne the formation of nodules was both rapidly and strictly re-adjusted to plant growth needs, allowing a full recovery. Our study suggested that a rapid re-launch of N acquisition, associated with a fine-tuning of nodule formation during the post-stress period is essential for efficient drought resilience in pea leading to yield stability.

Feature-shared adaptive-boost deep learning for invasiveness classification of pulmonary subsolid nodules in CT images.

In clinical practice, invasiveness is an important reference indicator for differentiating the malignant degree of subsolid pulmonary nodules. These nodules can be classified as atypical adenomatous hyperplasia (AAH), adenocarcinoma in situ (AIS), minimally invasive adenocarcinoma (MIA), or invasive adenocarcinoma (IAC). The automatic determination of a nodule's invasiveness based on chest CT scans can guide treatment planning. However, it is challenging, owing to the insufficiency of training data and their interclass similarity and intraclass variation. To address these challenges, we propose a two-stage deep learning strategy for this task: prior-feature learning followed by adaptive-boost deep learning. The adaptive-boost deep learning is proposed to train a strong classifier for invasiveness classification of subsolid nodules in chest CT images, using multiple 3D convolutional neural network (CNN)-based weak classifiers. Because ensembles of multiple deep 3D CNN models have a huge number of parameters and require large computing resources along with more training and testing time, the prior-feature learning is proposed to reduce the computations by sharing the CNN layers between all weak classifiers. Using this strategy, all weak classifiers can be integrated into a single network. Tenfold cross validation of binary classification was conducted on a total of 1357 nodules, including 765 noninvasive (AAH and AIS) and 592 invasive nodules (MIA and IAC). Ablation experimental results indicated that the proposed binary classifier achieved an accuracy of with an AUC of 81.3 . These results are superior compared to those achieved by three experienced chest imaging specialists who achieved an accuracy of , , and , respectively. About 200 additional nodules were also collected. These nodules covered 50 cases for each category (AAH, AIS, MIA, and IAC, respectively). Both binary and multiple classifications were performed on these data and the results demonstrated that the proposed method definitely achieves better performance than the performance achieved by nonensemble deep learning methods. It can be concluded that the proposed adaptive-boost deep learning can significantly improve the performance of invasiveness classification of pulmonary subsolid nodules in CT images, while the prior-feature learning can significantly reduce the total size of deep models. The promising results on clinical data show that the trained models can be used as an effective lung cancer screening tool in hospitals. Moreover, the proposed strategy can be easily extended to other similar classification tasks in 3D medical images.

P2.15-07 Bimanual Examination Is Indispensable in the Surgery of Lung Metastatic Tumors!

Thoracic computed tomography (Th CT) is used to evaluate the surgical outcome of lung metastatic tumors. However, Th CT is often inadequate on the detection of millimetric lesions and it alone is a problematic for guiding complete resection. It is recommended for complete resection that the intraoperative bimanual palpation of the lung to be used with care and meticulously. In addition, there are studies for minimally invasive surgical methods may be an alternative to thoracotomy where bimanual evaluation is not possible. In this study, we aimed to evaluate the number of radiological and pathological metastases in patients who underwent metastasectomy with muscle conservative thoracotomy (MCT). Between 2008 and 2018, 204 patients with metastatic lung tumors who underwent metastasectomy were included in the Department of Thoracic Surgery, Ankara University Faculty of Medicine. Preoperative Th CT imaging of all patients was evaluated in a multidisciplinary council. The relationship between the numbers of metastases detected by pathological examination of patients and the number of pulmonary nodules reported as 'metastasis' in preoperative Th CT was retrospectively analyzed. 55% (n: 111) of the patients were F, 45% (n: 93) were M, mean age was 46.4 (13-77). %25 (n:52) of two hundred and four patients had bilateral, 3% (n: 8) of the patients had 3 and 1% (n: 4) of the patients had 4 metastasectomy with MCT due to contralateral lung metastasis or re-metastasectomy. The number of pulmonary nodules detected in Th CT was 740 (mean: 2,6), although the number of pulmonary nodules resected was 1503 (mean: 5,29). In histopathological evaluation of these nodules, 1120 (mean: 3,94) were reported as metastases. 2,03 fold of the nodules detected in Th CT were detected by bimanual intraoperative examination and 1.5 fold of nodules detected in Th CT were pathologically assessed as metastasis. Primary tumor numbers and histologies of 1120 metastatic nodules respectively; 42% (n: 475) were epithelial tumors and 58% (n: 645) were mesenchymal tumors. In this study, 740 pulmonary nodules were reported in Th CT of 204 patients. However, 763 additional pulmonary nodules were detected by bimanual palpation. 49.8% (380/763) of 763 additional pulmonary nodules were metastatic. Although minimally invasive surgery is a successful method for the surgery of many thoracic malignancies, bimanuel palpation of the lung with open surgery is still an effective method for the complete resection of pulmonary metastases. Bimanual examination is indispensable especially in the pulmonary metastasectomy of sarcomas.

WS04.02 Challenges in Imaging Evaluation to Enter Data in the IASLC Database

Soon after the publication of the proposals for the 8thedition of the TNM staging system, the International Association for the Study of Lung Cancer (IASLC) opened a new database for data collection for the next iteration of the lung cancer staging system (1). The database contains more than 450 fields, which address data on patient characteristics, baseline laboratory values, as well as the results of pulmonary function, imaging, and pathological tests. As the database collects the data about lung cancer newly diagnosed between January 1, 2011, and December 31, 2019, the data entered might be predominantly retrospectively collected in some centers. From an imaging perspective, this might lead to a number of problems. First, at least some of the elements required by the database might not be mentioned in the radiological reports. This may necessitate a re-evaluation of the imaging studies by an experienced radiologist, which might not be possible in all centers. Furthermore, the levels of training of the radiologists and reporting across different countries may be variable and thus introduce some degree of imprecision into the quality of the data. As an example, in T staging, particular attention has to be paid to thorough measurements to ensure that the largest diameter in the axial, coronal, or sagittal plane is measured (2). Caution should also be taken not to overdiagnose additional pulmonary nodules as metastases. In N staging, particular attention has to be paid to the lymph node atlas-mining, particularly the well-known pitfall in the correct assignment of lymph nodes at levels 4 and 10 (3-5). Furthermore, the quality of imaging and the availability of more advanced/expensive imaging techniques may also vary from country to country. As an example, the availabilities of PET/CT and/or MRI are not homogenous all over the globe. However, if PET/CT is not performed routinely in operable patients, as many as 20% of unexpected distant metastases might be missed (6). Future staging projects should specifically address these issues in order to further improve the the quality of data necessary to improve the next iteration of the staging system. 1. Giroux DJ, Van Schil P, Asamura H, Rami-Porta R, Chansky K, Crowley JJ, et al. The IASLC Lung Cancer Staging Project: A Renewed Call to Participation. J Thorac Oncol. 2018;13(6):801-9. 2. Travis WD, Asamura H, Bankier AA, Beasley MB, Detterbeck F, Flieder DB, et al. The IASLC Lung Cancer Staging Project: Proposals for Coding T Categories for Subsolid Nodules and Assessment of Tumor Size in Part-Solid Tumors in the Forthcoming Eighth Edition of the TNM Classification of Lung Cancer. J Thorac Oncol. 2016. 3. El-Sherief AH, Lau CT, Obuchowski NA, Mehta AC, Rice TW, Blackstone EH. Cross-Disciplinary Analysis of Lymph Node Classification in Lung Cancer on CT Scanning. Chest. 2017;151(4):776-85. 4. El-Sherief AH, Lau CT, Wu CC, Drake RL, Abbott GF, Rice TW. International association for the study of lung cancer (IASLC) lymph node map: radiologic review with CT illustration. Radiographics. 2014;34(6):1680-91. 5. Aviram G, Revel MP. Misclassification of Lymph Nodes in Lung Cancer Staging: Can We Improve? Chest. 2017;151(4):733-4. 6. Fischer B, Lassen U, Mortensen J, Larsen S, Loft A, Bertelsen A, et al. Preoperative Staging of Lung Cancer with Combined PET-CT. N Engl J Med. 2009;361(1):32-9. staging, TNM, Lung cancer

TO DO OR NOT TO DO? THE CASE FOR PDL1 TESTING IN LOCALIZED HEAD AND NECK SQUAMOUS CELL CARCINOMA (HNSCC)

SESSION TITLE: Lung Cancer SESSION TYPE: Fellow Case Reports PRESENTED ON: 10/23/2019 8:45 AM - 9:45 AM INTRODUCTION: HNSCC is the 6th most common cancer with recurrence rate of over 50%. Multiple mechanisms have been identified by which tumor cells evade T-cell directed immunity. Expression of PDL1 is one of these mechanisms (1). The clinical role of PDL1 testing in localized HNSCC has not been defined in the literature given rising interest in use of immunomodulating agents to treat advanced cancer/metastasis. We present a case of localized HNSCC post excision which presented as metastasized recurrence in the lung (leading to demise of the patient). CASE PRESENTATION: 73-year-old female nonsmoker, asthmatic presented with chest pain for 3 days. PMH was significant for progressive shortness of breath and cough for 1 month treated as pneumonia, and moderately well differentiated P16 negative HNSCC of tongue (T2N0MO) s/p left partial glossectomy and ipsilateral neck dissection with clear margins and negative lymph nodes 1 year ago. On admission, patient was hemodynamically stable with SpO2 of 90% on room air. Physical exam findings revealed decreased right sided air entry with dullness to percussion. CXR was read as atelectasis of the right lung with right sided mediastinal shift. Chest CT revealed bilateral PE and a large right lower lobe and hilar mass with right paratracheal lymphadenopathy. Additional bilateral pulmonary nodules demonstrated cavitation. Bronchoscopy and EBUS yielded keratinizing, P16 negative squamous cell cancer (SqCC) involving right upper lobe, bronchus intermedius, hilar mass and Station 7 lymph node. Immunohistochemistry (IHC) showed high expression of PDL1 i.e. Tumor Proportion Score (TPS) of 91%. Given the heavy burden of SqCC in the lung, metastatic disease from the tongue was suspected. IHC testing of the tongue specimen was requested and revealed high expression of PDL1 with TPS of 75%. Therapy with paclitaxel, carboplatin and pembrolizumab was initiated and planned for every 3 weeks, however the patient soon expired. DISCUSSION: FDA has approved two immunomodulating agents for use in PDL1 positive recurrent or metastatic HNSCC. There is no clear guideline on the utility of PDL1 testing in localized HNSCC. This case highlights the need for future research in PDL1 testing in the subset of localized HNSCC to prevent similar fatal outcomes due to recurrence. CONCLUSIONS: Incorporation of testing PDL1 in localized HNSCC might lead to improved immunotherapy and recurrence rates. Reference #1: Forster MD, Devlin MJ. Immune Checkpoint Inhibition in Head and Neck Cancer. Front Oncol. 2018;8:310. Published 2018 Aug 29. https://doi.org/10.3389/fonc.2018.00310 DISCLOSURES: No relevant relationships by Muhammad Ali, source=Web Response No relevant relationships by Mary Jo Farmer, source=Web Response

Morphometric analysis and characterization of the nutritional quality in African yam bean accessions

Underutilized crops with rich nutritional base in addition to high seed yield are currently promoted in reducing hunger and malnutrition ravaging Africans. Identifying specific accessions with rich genetic bases provide information for developing biofortified legumes. Fourteen morphological and two nutritional traits of 23 African yam bean accessions were assessed under a replicated field trial in one location over 4 years. Analysis of variance revealed significant variations for most traits with high genotypic correlation coefficients. Genotypic coefficient of variation was high for maturity date (59.95%), protein content (60.78%), tuber yield per plant (67.33%) and number of seeds per pod (77.22%). Seed yield did not correlate with protein and oil content, indicating that nutritional traits were independent of seed yield traits. Heritability was high for most traits but moderate for protein and oil content. First order predictor variables, identified number of seeds per pod, and pod traits to directly affect seed and tuber yield. First seven principal components axes explained 67% of total variation including nutritional traits. Four distinct accession clusters at the R-squared distance of 0.45 similarity index were identified. Simultaneous improvement in earliness, yield, protein and oil contents are achievable by selecting parents from clusters I and II. The only accession in cluster III (TSs12) produced nodules in addition to average seed yield, protein and oil content, and could be selected for cultivation in nitrogen deficient soils. Wide diversity in these accessions can be maximized for developing acceptable African yam bean varieties with enhanced yield and nutritional value.

26. ANCA-associated vasculitis in a patient with a PET-avid lung lesion

IntroductionVasculitis can be a primary or secondary process. Underlying secondary causes include infection, malignancy and other autoimmune conditions. This case describes a patient with findings consistent with ANCA-associated vasculitis. As part of investigations, she was identified as having a PET-avid lung lesion for which she is currently undergoing further investigation via the respiratory team. From a rheumatological perspective she is receiving treatment for her vasculitis, however at present it is unclear whether this is a secondary paraneoplastic phenomenon. This case explores the nature of her presentation and the relationship of primary versus secondary paraneoplastic vasculitis.Case descriptionA 75-year-old lady presented to hospital with a 6-week history of fatigue, pyrexia and myalgia. During this period she additionally noted numbness/neuropathic pains affecting her feet. She had a background of COPD/asthma diagnosed 10 years previously. She had additionally undergone polypectomy for nasal-polyps and had underwent right mastectomy in 1990 for breast cancer.She was noted to have raised inflammatory markers (CRP 256) and eosinophilia. She was deemed to have an infective exacerbation of COPD/asthma although at the time she had limited respiratory symptoms and CXR was reported normal. She was initiated on a 5-day course of prednisolone 40mg and antibiotics. Her symptoms appeared to respond to treatment, as did her CRP and eosinophilia, and she was discharged.Unfortunately she re-presented with similar symptoms within a few days. Further investigation and blood tests demonstrated cANCA antibodies with PR3 of 128 IU. Urine PCR was mildly raised at 30mg/mmol. She was reviewed by the rheumatology team, and likely diagnosis of ANCA-associated vasculitis was made. It was noted however that while her serology was suggestive of granulomatosis with polyangiitis (GPA), her clinical picture of eosinophilia, COPD/asthma and nasal-polyps was more consistent with eosinophilic granulomatosis with polyangiitis (EGPA). She was re-initiated on prednisolone 40mg and demonstrated clinical response.As part of work-up, CT-CAP was arranged. This reported a spiculated lesion of the right-upper lung lobe with appearances concerning for malignancy. Subsequent PET-CT confirmed this be PET-avid, with additional suspicious nodules. She was additionally arranged for nerve-conduction studies regarding her feet symptoms, with findings being consistent with mononeuritis multiplex.From a rheumatological perspective, she has been initiated on azathioprine and prednisolone is gradually being reduced. She has ongoing follow up with respiratory regarding her lung lesion, with initial biopsy being inconclusive. Further attempt at gaining histology is currently awaited.DiscussionFrom a rheumatological perspective, aspects of this case support a diagnosis of ANCA-associated vasculitis. Presence of cANCA with PR3 antibodies are typically associated with GPA, although her eosinophilia, asthma and previous history of nasal polyps would be more consistent with EGPA. The features of mononeuritis multiplex on nerve conduction studies would also support an underlying diagnosis of vasculitis.Although there is a documented relationship between malignancy and vasculitis, this appears to be relatively rare with a 5-8% association. Haematological malignancies such as lymphoma and MDS have a greater association in comparison to solid tumours. Typical manifestation of paraneoplastic vasculitis is that of cutaneous involvement, particularly of leukocytoclastic vasculitis. Reports suggest improvement of secondary vasculitis on treatment of the underlying condition.With regards to the association of ANCA-vasculitis and solid tumour malignancy, cases appear to be less well-described. The majority of case studies exploring the link between these conditions are primarily in the context of secondary malignancy occurring after immunosuppressive therapy (such as cyclophosphamide) for vasculitis. Review of literature outside of this context, especially in regards of specifically lung malignancy is limited – so a consistent established link may be less apparent. Of the limited studies, interestingly there have been reports of patients with biopsy proven lung malignancy and raised MPO/PR3, with levels normalising following treatment of the underlying lesion.As described in this case, our patient currently awaits further investigation regarding her lung lesion and subsequent review of its definitive intervention. Should investigations confirm malignancy and this be treated, then it would be interesting to see whether there is clinical resolution of her systemic vasculitis secondary to this.Key learning pointsThis case demonstrates the presence of 2 conditions of ANCA-associated vasculitis and possible lung malignancy which were both diagnosed during the same admission. Literature suggests possible association between vasculitis and malignancy in a general sense, however specific description of ANCA-vasculitis and lung malignancy has been rarely described.At present, this patient’s vasculitis is being managed whilst definitive intervention is being arranged for her underlying lung lesion. Continued follow up from both the rheumatologists and respiratory team is ongoing and response of her condition will be assessed pending intervention of her underlying lung lesion.Conflicts of interestThe authors have declared no conflicts of interest.

IOUS and CE-IOUS during hepatic resection for patients with hepatocellular carcinoma in liver cirrhosis1.

To retrospectively evaluate the role of intraoperative ultrasonography (IOUS) and contrast-enhanced IOUS (CE-IOUS) for the patients with hepatocellular carcinoma (HCC) undergoing hepatic resection (HR). Twenty-one consecutive patients who had undergone HR for HCC were included in this study. The patients were subject to preoperative imaging modalities including preoperative ultrasonography (Pre-US) and preoperative contrast-enhanced ultrasonography (Pre-CEUS). All the patients then underwent intraoperative ultrasonography (IOUS) and contrast-enhanced intraoperative ultrasonography (CE-IOUS) during surgery. The visualization of primary HCC and additional lesions of all patients were analyzed. Twenty-one HCCs were detected during Pre-US and the remaining six lesions (28.6%) were detected during IOUS and CE-IOUS. Thus the treatment plan was changed in 28.6% of patients. Twenty-one HCCs (diameter, 0.6-3.0 cm; mean±SD, 1.98±0.85 cm) were measured on Pre-US and remeasured on IOUS (diameter, 0.9-3.3 cm; mean±SD, 2.19±0.84 cm) (p < 0.001). The 6 additional lesions consisted of three moderately differentiated HCCs, one cholangiocarcinoma (ICC), and two high-grade dysplastic nodules (DNs). The mean maximal diameter of the 6 additional lesions was 0.83 cm (range: 0.6-1.1 cm). The malignancy associated features such as capsule interruption, echo heterogeneity, hypo-echoic rim, and a nodule in nodule pattern were more often depicted on IOUS than on Pre-US (all p < 0.01). On CEUS, 19 (90.5%) of 21 HCCs were hyper-enhanced in the arterial phase and washed out from the portal phase to the late phase; the remaining two (9.5%) were hypoenhanced. On CE-IOUS, tumor vasculatures were classified as four patterns: 11 (52.4%) exhibited netlike pattern, 7 (33.3%) annular pattern, 2 (9.5%) mixed pattern, and 1 (4.8%) radial pattern. 3 mHCCs and 2 DNs of six additional nodules had similar greyscale imagining features on IOUS, but they showed different enhancement patterns on CE-IOUS. The ICC showed slightly heterogeneous enhancement during the arterial phase and hypo-enhancement during the portal phase. IOUS detects more lesions and the treatment plan is changed in 28.6% of patients. HCCs were larger on IOUS than on Pre-US. The typical imaging features of HCCs were better depicted on IOUS in comparison with Pre-US. CE-IOUS can catch the details of microcirculation perfusion of HCCs more sensitively than CEUS. Both IOUS and CE-IOUS were able to provide more decision information during surgery.

The formation mechanisms of sedimentary pyrite nodules determined by trace element and sulfur isotope microanalysis

Redox sensitive trace elements in pyrite, including nodules, are increasingly used to infer the chemical conditions of ancient oceans - but considerable uncertainty remains regarding the mechanism and timing of nodule formation. Resolving these uncertainties is important because pyrite nodules must form in connection with the overlying water column, rather than during late diagenesis, to reflect the composition of the global ocean. Existing models for pyrite nodule formation have been specific to pyrite textures from individual sites, and we lack a unified model that can explain the compositional and textural diversity observed in nodules from different localities. In this study we examine ten pyrite nodules from several geological periods (Neoarchean to Carboniferous) using in situ LA-ICP-MS and SHRIMP-SI analyses. We present transects of spot analyses of trace elements (As, Ag, Cu, Co, Ni, Sb and Se) and S isotope ratios for each nodule. The pyrite nodules can be classified according to three main categories: those with (1) little to no trace element or isotopic zonation of the nodule from core to margin, (2) strong zonation from core to margin, and (3) minor zonation near the core but more significant zonation near the margin of the nodule. We further illustrate this zonation with a NanoSIMS element map from an additional pyrite nodule. These results are interpreted to indicate nodule formation along a spectrum between two end-member mechanisms. We suggest that the absence of trace element or isotopic zonation reflects nodule growth by a pathway that is analogous to the pervasive growth mechanism for carbonate nodules. This model involves the production of many nucleation sites that are evenly distributed within the volume that the nodule eventually occupies. Consequently, this mechanism results in a chemically homogenous nodule. Pyrites formed this way are suitable for paleoceanographic reconstruction. The other end-member mechanism is analogous to the concentric growth model for carbonate concretions. In this scenario, the core of the nodule forms first and is followed by the addition of concentric layers - each with a progressively different trace element content and δ34S signature as diagenesis progresses. Despite having limited utility for reconstructing ancient seawater, these late forming nodules may track the evolving availability of bioessential trace elements for the subsurface biosphere with important implications for global biogeochemical cycles. Spatial trends in trace elements and S isotopes thus speak to the mechanisms of pyrite nodule formation and provide a framework for evaluating nodule suitability for a range of paleoenvironmental studies.

Prevalence of pulmonary nodules in dogs with malignant neoplasia as determined by CT.

In order to estimate the prevalence of pulmonary nodules in dogs with nonpulmonary malignant neoplasia, medical record descriptions of CT findings in dogs diagnosed with nonpulmonary malignant neoplasia were reviewed retrospectively. A total of 536 dogs were sampled from a single hospital. For malignant neoplasms with>10 affected individuals, prevalence of multiple pulmonary nodules at first CT was hemangiosarcoma 24 of 58 (41%), osteosarcoma 14 of 55 (26%), carcinoma 20 of 80 (25%), histiocytic sarcoma five of twenty-one (24%), soft tissue sarcoma 13 of 57 (23%), adenocarcinoma 11 of 60 (18%), melanoma five of thirty-seven (14%), lymphoma 10 of 76 (13%), mast cell tumor two of forty-seven (4%), and squamous cell carcinoma zero of seventeen (0%). A solitary pulmonary nodule was identified at first CT in 33 (6%) dogs. Of these, nine had follow-up CT, including two dogs in which the nodule disappeared, three dogs in which the size of the nodule did not change, and four dogs in which the nodule enlarged and additional pulmonary nodules appeared. Dogs with hemangiosarcoma were most likely to have signs of pulmonary metastasis at first CT, whereas dogs with mast cell tumor were infrequently affected, and no dog with squamous cell carcinoma had signs of pulmonary metastasis. A solitary pulmonary nodule at first CT was an indeterminate finding, potentially unassociated with neoplasia.

Partial Splenectomy in a Case of Granulosa Cell Tumour (GCT) with Isolated Splenic Metastasis: A Case Report with Review of Literature

A 50-year-old female, a case of granulosa cell tumour of the ovary, operated multiple times, post-chemotherapy and hormonal therapy, since the last 12 years was detected to have a splenic parenchymal metastasis on follow-up. Owing to poor results with our experience with total splenectomy on two postoperative cases of ca ovary, we decided to perform partial splenectomy. Intraoperatively, the nodule was localised with intra-op USG, during which two additional nodules were found and excised. Final histopathology showed tumour in two of these nodules. Intra-op USG-guided RFA of the spleen lesions with minimally invasive techniques was another option but since the patient had a concomitant incisional hernia we decided to proceed with open approach along with hernioplasty. In English literature, spleen as the only site of metastasis is exceedingly rare. We report the first case of granulosa cell tumour of the ovary which has been treated with partial splenectomy. Carrying out this case successfully leads us to believe that partial splenectomy is a viable option in cases where spleen is the only site of metastasis, which also protects the patient from possible complications of splenectomy.

Additional nodules detected in EOB-MRI in a patient with single resectable hepatocellular carcinoma : Still indicated for surgical resection?

Additional nodules detected in EOB-MRI in a patient with single resectable hepatocellular carcinoma : Still indicated for surgical resection?

Value of PET/MRI for assessing tumor resectability in NSCLC-intra-individual comparison with PET/CT.

The purpose of this study was to compare the diagnostic accuracy of positron emission tomography (PET)/MRI with PET/CT for determining tumor resectability of non-small cell lung cancer (NSCLC). Sequential trimodality PET/CT/MRI was performed in 36 patients referred with the clinical question of resectability assessment in NSCLC. PET/CT and PET/MR images including T1 weighted sequence (T1-Dixon) and respiration gated T2 weighted sequence (T2-Propeller) were evaluated for resectability-defining factors; i.e. longest diameter of the tumor, minimal tumor distance to the carina, mediastinal invasion, invasion of the carina, pleural infiltration, pericardial infiltration, diaphragm infiltration, presence of additional nodules. There was no significant difference of maximal axial diameter measurements of the primary lung tumors and narrow limits of agreement in Bland-Altman analysis ranging from -11.1 mm to + 11.8 mm for T2-Propeller and from -14.3 mm to + 13.8 mm for T1-Dixon sequence. A high agreement of PET/MR with PET/CT for the different resectability-defining factors was observed (k from 0.769 to 1.000). There was an excellent agreement of T2-Propeller sequence and CT for additional pulmonary nodule detection (k of 0.829 and 0.833), but only a moderate and good agreement using T1-Dixon sequence (k of 0.484 and 0.722). In NSCLC the use of PET/MRI, including a dedicated pulmonary MR imaging protocol, provides a comparable diagnostic value for determination of tumor resectability compared to PET/CT. Our findings suggest that whole body PET/MRI can safely be used for the local staging of NSCLC patients. Further studies are warranted to determine whether it is feasible to integrate an imaging sequence in a whole body PET/MRI setting with the potential advantage of detection of liver or brain metastases.